Established in mid-1943 as a B-24 Liberator heavy bomb squadron; trained under Second Air Force. Deployed to the Mediterranean Theater of Operations (MTO) in January 1944, being assigned to Fifteenth Air Force in Southern Italy.

Engaged in very long range strategic bombardment missions against enemy strategic targets in Italy, France, Germany, Austria, Czechoslovakia, Hungary, and the Balkans until April 1945. Bombed aircraft factories, assembly plants, oil refineries, storage areas, marshalling yards, airdromes, and other objectives until the German Capitulation in May 1945.

Most of squadron was demobilized in Italy in May 1945; returning to United States with skeleton staff. Re-equipped and redesignated a B-29 Superfortress very heavy bomb squadron, and received new personnel. Began training under Second Air Force for planned deployment to the Western Pacific Area (WPA), however Japanese Capitulation in August led to inactivation of squadron in October.

Reactivated in 1947 as a reserve Strategic Air Command B-29 Superfortress squadron; activated in 1951 and squadron aircraft and personnel being sent to Far East Air Forces Bomber Command as replacements. Squadron inactivated after personnel and equipment were deployed. Became a Tactical Air Command reserve Troop Carrier squadron shortly afterward; equipped with surplus C-46 Commandos. Personnel and equipment over by 403d Troop Carrier Wing and inactivated.

Reactivated under Strategic Air Command in 1963, replacing provisional B-52H Stratofortess squadron at Columbus AFB, Mississippi. Performed intercontinental training and deployments, also standing nuclear alert. Beginning in 1966, squadron deployed personnel to forward bases in the Western Pacific, where they engaged in combat missions over Indochina as part of Operation Arc Light.

Inactivated in 1969 when SAC pulled out Columbus and the base became an Air Training Command pilot training base